Carboxylic acid interconversions

Acidity of Amides, Imides, and Sulfonamides Characteristic Reactions Reaction with Water Hydrolysis Reaction with Alcohols Reactions with Ammonia and Amines Reaction of Acid Chiorides with Salts of Carboxylic Acids Interconversion of Functional Derivatives Reactions with Organometallic Compounds 18.10 Reduction... 

Figure 21.2 Interconversions of carboxylic acid derivatives. A more reactive acid derivative can be converted into a less reactive one, but not vice versa.

This chapter covers not only nuclear and extranuclear quinoxahnecarboxylic acids (and anhydrides) but also the carboxylic esters, acyl halides, carboxamides, carbohydrazides, carbonitriles, carbaldehydes, and (ketonic) acyl derivatives of quinoxaline a few related speceis are also included. To avoid repetition, the interconversions of these quinoxaline derivatives are discussed only at the first opportunity thus the esterification of quinoxalinecarboxylic acids in covered as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, appropriate cross-references have been inserted. 

Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

When a multistep synthesis is being undertaken with other sensitive functional groups present in the molecule, milder reagents and reaction conditions may be necessary. As a result, many alternative methods for effecting interconversion of the carboxylic acid derivatives have been developed and some of the most useful reactions are considered... 

The broad and nearly universal applicability of the cinchonan carbamate CSPs for chiral acid separations is further corroborated by successful enantiomer separations of acidic solutes having axial and planar chirality, respectively. For example, Tobler et al. [124] could separate the enantiomers of atropisomeric axially chiral 2 -dodecyloxy-6-nitrobiphenyl-2-carboxylic acid on an C-9-(tert-butylcarbamoyl)quinine-based CSP in the PO mode with a-value of 1.8 and Rs of 9.1. This compound is stereolabile and hence at elevated temperatures the two enantiomers were interconverted during the separation process on-column revealing characteristic plateau regions between the separated enantiomer peaks. A stopped-flow method was utilized to determine the kinetic rate constants and apparent rotational energy barriers for the interconversion process in the presence of the CSP. Apparent activation energies (i.e., energy barriers for interconversion) were found to be 93.0 and 94.6 kJ mol for the (-)- and (-l-)-enantiomers, respectively. 

Furazan- and furoxan-carboxylic acids are thermally and hydrolytically unstable decomposing to a-(hydroxyimino)nitriles, but their amide, ester, halide, and nitrile derivatives are readily accessible and all undergo the expected functional group interconversions. Dicyanofuroxan reacts with hydroxylamine to give the fused oxazino compound (63) and the pyridazino analogue (64) is similarly formed with hydrazine <82H(19)1063>. 

The chroman ring system is stable to organometallic reagents, for example in the formation of the tertiary alcohol (690) in high yield (63HCA650), and to the usual interconversion of carboxylic acid, acyl chloride, carboxamide and nitrile. 

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